Synthesis and Structure-activity Relationship of Disubstituted Benzamides as a Novel Class of Antimalarial Agents

Malaria is a devastating world health problem. Using a compound library screening approach, a novel series of disubstituted benzamide compounds was identified to have significant activity against malaria strains 3D7 and K1.  These compounds represent a new antimalarial molecular scaffold, which demonstrate EC₅₀ values of 60 and 430 nM against strains 3D7 and K1, respectively.  Herein we report our findings on the efficient synthesis, structure-activity relationships, and biological activity of this new class of antimalarial agents.